The Function of NR1D2
Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle.
Protein names
Recommended name:
Nuclear receptor subfamily 1 group D member 2Short name:
RVRAlternative name(s):
Orphan nuclear hormone receptor BD73Rev-erb alpha-related receptor
Rev-erb-beta
V-erbA-related protein 1-related
EAR-1R
- RS6800768 (NR1D2) ??
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Top Gene-Substance Interactions
Substances That Increase NR1D2
| Substances | Interaction | Organism | Category |
Substances That Decrease NR1D2
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Widely expressed. Expressed at high levels in the liver, adipose tissue, skeletal muscle and brain. Expression oscillates diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in peripheral tissues.
Gene Pathways:
Enzyme Regulation:
The heme-bound form can bind gaseous signaling molecules such as CO and nitric oxide (NO) and NO can reverse its transcriptional repressor activity.
Molecular Function:
- Core Promoter Sequence-Specific Dna Binding
- Steroid Hormone Receptor Activity
- Rna Polymerase Ii Transcription Factor Activity, Ligand-Activated Sequence-Specific Dna Binding
- Zinc Ion Binding
Biological Processes:
- Regulation Of Transcription, Dna-Templated
- Transcription Initiation From Rna Polymerase Ii Promoter
- Regulation Of Lipid Metabolic Process
- Regulation Of Circadian Rhythm
- Negative Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription, Dna-Templated
- Rhythmic Process
- Regulation Of Inflammatory Response
- Lipid Homeostasis
- Regulation Of Energy Homeostasis
- Regulation Of Skeletal Muscle Cell Differentiation